Biomarkers Associated With Spontaneous Preterm Birth Less Than 32 Wks Gestation

Preterm delivery (PTD) is a leading cause of neonatal mortality and continues to be a major
public health concern, reaching 12.9% in 2006, despite intense research to reverse this
trend. Currently, fetal fibronectin (fFN) screening and cervical length determined by
ultrasound are two tests which are proven to have benefit in the identification of those at
greatest risk for preterm delivery. However the benefit of these tests is limited to
situations where a negative result can avoid unnecessary interventions. The first goal of
this study is to identify non-invasive predictor(s) that will increase the clinician's
ability to identify patients who present with second trimester preterm labor (PTL) at risk
for preterm delivery (PTD) ≤ 32 weeks gestation.

Currently, maternal fetal monitoring is limited, as it is difficult to "see" what is going on
in the placenta (maternal-fetal interface) without invasive measures such as placental biopsy
or amniocentesis. Our preliminary study from term pregnancies has shown that a specific
correlation of an intrauterine cytokine may be reflected in one noninvasive site but not
another, depending upon the type of cytokine and the compartment from which it is secreted.
Therefore, our second goal for this study is to identify inflammatory markers in non-invasive
maternal compartments (such as saliva, blood, urine, and/or cervical and vaginal secretions)
that have a strong association with placenta/fetal membranes at the time of preterm birth ≤
32 weeks gestation.

Pregnant women, under 32 weeks gestation, who are admitted to Winthrop University Hospital
for evaluation of preterm labor will be eligible for this study. Women with indicated preterm
births (i.e. pre-eclampsia), multiple pregnancies, known major fetal abnormality (ex. those
that are known to be incompatible with life) and premature rupture of membranes will be
excluded from this study. After consent is obtained, samples (blood, urine, saliva, vaginal,
and cervical secretions) will be obtained and biomarkers will be identified using a Bio-Plex
cytokine concentration assay. These women will than be followed until they deliver. Women who
deliver after 32 weeks gestation will form our control group and women who deliver before 32
weeks gestation will form our preterm birth group. Concentration of the biomarkers in the
various maternal-fetal compartments will be analyzed and compared between the two groups. For
all women who delivery ≤ 32 weeks gestation, non-invasive samples will also be collected
around delivery and these cytokine levels will be compared to placenta/fetal membranes to
access how well non-invasive fluids reflect the intrauterine environment.

We hypothesize that preterm labor will display an inflammatory profile, which consists of
unique inflammatory biomarkers from different non-invasive bodily fluid compartments (such as
Il-10 in urine, VEGF in cervical secretions, and IP-10 in saliva), that correlates with a
high incidence of preterm birth.

Inclusion Criteria:

- Pregnant women age 18-40 years old between 20 to 32 weeks gestation with singleton
pregnancies and are admitted to Winthrop University Hospital for evaluation of preterm
labor. Preterm labor will be defined as contractions every 5 minutes associated with
cervical changes or cervical dilatation > 2cm with 80% effacement. Subjects must have
reliable dates confirmed by early ultrasound.

Exclusion Criteria:

- Indicated preterm births (i.e. pre-eclampsia), multiple pregnancies, known major fetal
abnormality (ex. those that are known to be incompatible with life) and premature
rupture of membranes.